| ObjectiveBy cross-sectional study, to investigate distribution of the allele and genotype frequency of FgBβ1689T/G,I6I/D,345C/T and HinfIA/C; To study impact of their polymorphisms and haplotypes on Fg concentration and molecular function. By case-control study, to analyze the relationship of their polymorphisms,haplotypes, Fg concentration and molecular function with cerebral infarction.MethodsThe study consisted of two parts. In the first part,1625 subjects for health check were collected with cross-sectional method from Kailuan Group. In the second part, A case-control study was designed, consisting of 96 cases and 107 controls.Cases were first onseting subjects with ACI from Department of Neurology in Kailuan Hospital.The healthy control subjects were volunteers recruited from individuals for healthy check in Kailuan Hospital. For all individuals, physical examination and quenstionaire were conducted by trained interviewers, and the venous blood on empty stomach in the early morning was collected. Biochemistry indicators including blood glucose,uric acid and total cholesterol were measured; Fg concentration,fibrin monomer polymerized velocity(FMPV),absorbance maximum(Amax) and FMPV/Amax were measured by computer assisted and automatic measurement system of plasma Fg feature; Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism and Sequencing methods. Results1. In the first part,the frequencies of the T1689 and G1689 were 84.7%, 15.3%,respectively;II6 and DI6,81.7%,18.3%;C345 and T345, 81.7%,18.3%;AHinfI and CHinfI,88.2%,11.8%.All polymorphism loci were in Hardy-Weinberg equilibrium.BβI6I/D and 345C/T were in perfect linkage disequilibrium;Bβ1689T/G with I6I/D and 345C/T were in strong linkage disequilibrium;But BβHinf IA/C with 1689T/G,I6I/D and 345C/T were weak,they were randomly distributed.There were no significant differences between the two genotype groups of Bβ1689T/G, I6I/D ,345C/T and HinfIA/C in terms of Fg concentration,FMPV,Amax and FMPV/Amax(P>0.05);But FMPV/Amax was significantly different between gender(P<0.05);In non-hypertension group,FMPV/Amax was higher in AA genotype than in CC+AC of BβHinfI(P<0.05),and in non-CI group,FMPV/Amax was higher in GG+TG genotype than in TT of Bβ1689(P<0.05).2. In the second part,there were no sinificant differences between CI group and control in terms of genotype and allele frequencies(P>0.05). FMPV and Amax were significantly higher in CI group than in control(P<0.01).In control,FMPV and Amax was higher in AC+CC genotype than that in AA of HinfI (P<0.05).In CI group,Amax was higher in TG+GG genotype than that in TT of 1689 (P<0.05).Between CI group and control,no differences were found in haplotype frequencies of H1,H4,H5 and H7(χ2=1.95,P>0.05),consisting of four polymorphism loci.Conclusions1. The linkage disequilibrium between I6I/D and 345C/T was perfect; 1689T/G with I6I/D and 345C/T,strong; But Hinf IA/C with 1689T/G,I6I/D and 345C/T,weak and random.2. FgBβ1689 in special condition can take part in and regulate functional expression of Fg molecular reactivity. There was no impact of I6 and 345 on Fg molecular function.3. Variation of HinfIA/C may make Fg molecular function low. But with hypertension ,there was no role.4. In four polymorphisms,only variational genotype of HinfI can promot expression of FMPV and Amax, and Ones with variational genotype of HinfI may be inclined to have much too risk of CI onset. There was no association of 1689,I6 and 345 with CI.5. There was no association between CI and major haplotypes of H1,H4,H5 and H7 composed of four polymorphisms, but they can influence functional expression of plasma fibrinogen concentration. |
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